The hypothesis that the pancreatic beta cell is a primary site of pathology in human and experimental diabetes, and the knowledge that the beta cell population affected by genetic background and responds to immunologic and toxic agents, has directed our attention to the need for further study of spontaneous models of diabetes mellitus. This request is for support to study the etiology and pathogenesis of diabetes in a unique model of insulin-dependent diabetes, the Bio Breeding Worcester (BB/W) rat. Support is requested for breeding and related experiments designed to establish inbred lines of diabetic BB/W rats and to define the genetic basis of the syndrome. Support is requested for ultrastructural and immunecytochemical studies of the evolving pancreatic islet and thyroid lesions designed to clarify the pathogenesis of these inflammmatory lesions. The possibility of an immunologic pathogenesis will be explored in islet and thyroid transplantation experiments. Other projects will study the effects of thymus and neonatal bone marrow transplantation, blood transfusions and the transfer of Concanavalin-A stimulated spleen cells between diabetic-prone and resistant animals. Support is also requested for funds to produce BB/N rats for distribution to other established investigators.